Thoracic impedance detection with blood resistivity compensation

ABSTRACT

This document discusses, among other things, a cardiac rhythm management device or other implantable medical device that uses thoracic impedance to determine how much fluid is present in the thorax, such as for detecting or predicting congestive heart failure, pulmonary edema, pleural effusion, hypotension, or the like. The thoracic fluid amount determined from the thoracic impedance is compensated for changes in blood resistivity, which may result from changes in hematocrit level or other factors. The blood-resistivity-compensated thoracic fluid amount can be stored in the device or transmitted to an external device for storage or display. The blood-resistivity-compensated thoracic fluid amount can also be used to adjust a cardiac pacing, cardiac resynchronization, or other cardiac rhythm management or other therapy to the patient. This document also discusses applications of the devices and methods for predicting or indicating anemia.

TECHNICAL FIELD

This document pertains generally to implantable medical devices and moreparticularly, but not by way of limitation, to congestive heart failure(CHF) thoracic fluid detection and other thoracic impedance systems,devices, or methods that compensate or correct for changes in bloodresistivity.

BACKGROUND

Variations in how much fluid is present in a person's thorax can takevarious forms and can have different causes. Eating salty foods canresult in retaining excessive fluid in the thorax and elsewhere. Posturechanges can also affect the amount of thoracic fluid. For example,moving from supine to standing can shift intravascular fluid away fromthe thorax toward the lower extremities.

Another example is pulmonary edema, which results in buildup ofextravascular fluid in the lungs. In pulmonary edema, fluid accumulatesin extracellular spaces, such as the spaces between lung tissue cells.One cause of pulmonary edema is congestive heart failure (CHF), which isalso sometimes referred to as “chronic heart failure,” or as “heartfailure.” CHF can be conceptualized as an enlarged weakened portion ofheart muscle. The impaired heart muscle results in poor cardiac outputof blood. As a result of such poor blood circulation, blood tends topool in blood vessels in the lungs. This intravascular fluid buildup, inturn, results in the extravascular fluid buildup mentioned above. Insum, pulmonary edema can be one important condition associated with CHF.

Yet another example of thoracic fluid accumulation is pleural effusion,which is the buildup of extravascular fluid in the space between thelungs and the rib cage. Pleural effusion can also result from CHFbecause, as discussed above, intravascular fluid buildup can result inthe extravascular interstitial fluid buildup. The extravascular fluidbuildup of pulmonary edema can, in turn, result in the extravascularfluid buildup of pleural effusion.

CHF may also activate several physiological compensatory mechanisms.Such compensatory mechanisms are aimed at correcting the reduced cardiacoutput. For example, the heart muscle may stretch to increase itscontractile power. Heart muscle mass may also increase. This is referredto as “hypertrophy.” The ventricle may also change its shape as anothercompensatory response. In another example, a neuro-endocrine responsemay provide an adrenergic increase in heart rate and contraction force.The Renin-Angiotensin-Aldosterone-System (RAAS) may be activated toinduce vasoconstriction, fluid retention, and redistribution of bloodflow. Although the neuro-endocrine response is compensatory, it mayoverload the cardiovascular system. This may result in myocardialdamage, and may exacerbate CHF.

Diagnosing CHF may involve physical examination, electrocardiogram(ECG), blood tests, chest radiography, or echocardiography. Managing aCHF patient is challenging. CHF may require potent drugs. Moreover,treatment may be thwarted by the compensatory mechanisms, which mayrecompensate for the presence of the medical treatment. Therefore,treating CHF involves a delicate balance to properly manage thepatient's hemodynamic status in a state of proper compensation to avoidfurther degeneration.

However, this delicate balance between compensation and effective CHFtreatment is easily upset, even by seemingly benign factors, such ascommon medication (e.g., aspirin), physiological factors, excitement, orgradual progression of the disease. This may plunge the patient into adecompensation crisis, which requires immediate corrective action so asto prevent the deterioration of the patient's condition which, if leftunchecked, can lead to death. In sum, accurately monitoring the symptomsof CHF, such as thoracic fluid accumulation, is very useful for avoidingsuch a decompensation crisis and properly managing the CHF patient in astate of relative well-being.

BRIEF DESCRIPTION OF THE DRAWINGS

In the drawings, which are not necessarily drawn to scale, like numeralsdescribe substantially similar components throughout the several views.Like numerals having different letter suffixes represent differentinstances of substantially similar components. The drawings illustrategenerally, by way of example, but not by way of limitation, variousembodiments discussed in the present document.

FIG. 1 is a block diagram illustrating generally one example of a systemthat provides a thoracic fluid amount indication that is adjusted tocompensate for a change in blood resistivity, if any.

FIG. 2 is a schematic illustration of one example in which portions ofthe system are implemented in an implantable cardiac rhythm management(CRM) or other implantable medical device (IMD).

FIG. 3 is a block diagram illustrating generally another example inwhich portions of the system are implemented in an implantable CRM orother IMD.

FIG. 4 is a flow chart illustrating generally one example of a method ofproviding a thoracic fluid amount indication that is compensated for anychanges in blood resistivity.

FIG. 5 is a flow chart illustrating generally one example of a method ofdetecting anemia using a blood impedance measurement performed by animplantable medical device.

DETAILED DESCRIPTION

The following detailed description includes references to theaccompanying drawings, which form a part of the detailed description.The drawings show, by way of illustration, specific embodiments in whichthe invention may be practiced. These embodiments, which are alsoreferred to herein as “examples,” are described in enough detail toenable those skilled in the art to practice the invention. Theembodiments may be combined, other embodiments may be utilized, orstructural, logical and electrical changes may be made without departingfrom the scope of the present invention. The following detaileddescription is, therefore, not to be taken in a limiting sense, and thescope of the present invention is defined by the appended claims andtheir equivalents.

In this document, the terms “a” or “an” are used, as is common in patentdocuments, to include one or more than one. In this document, the term“or” is used to refer to a nonexclusive or, unless otherwise indicated.Furthermore, all publications, patents, and patent documents referred toin this document are incorporated by reference herein in their entirety,as though individually incorporated by reference. In the event ofinconsistent usages between this document and those documents soincorporated by reference, the usage in the incorporated reference(s)should be considered supplementary to that of this document; forirreconcilable inconsistencies, the usage in this document controls.

In this document, the term intravascular includes the term intracardiac.

In this document, the term cardiovascular includes an association witheither the heart or a blood vessel.

In this document, the term “thorax” refers to a human subject's bodyother than the subject's head, arms, and legs.

FIG. 1 is a block diagram illustrating generally one example of a system100 that provides an indication of the amount of fluid in the thorax(“thoracic fluid indication”) that is adjusted to compensate for achange in blood resistivity, if any. In this example, the system 100includes a thoracic impedance measurement circuit 102. The thoracicimpedance measurement circuit 102 receives at least one electricalsignal from electrodes associated with a patient's thorax. Thiselectrical signal is typically received in response to a test energyapplied to the thorax, such as by a thoracic impedance test energydelivery circuit 104.

One illustrative example of some electrode configurations and circuitsfor performing thoracic impedance measurements is described in Hartleyet al. U.S. Pat. No. 6,076,015 entitled RATE ADAPTIVE CARDIAC RHYTHMMANAGEMENT DEVICE USING TRANSTHORACIC IMPEDANCE, which is assigned toCardiac Pacemakers, Inc., and which is incorporated herein by referencein its entirety, including its description of performing thoracicimpedance measurements. The Hartley et al. U.S. Pat. No. 6,076,015 usesthoracic impedance to obtain a respiration signal. By contrast, thepresent patent application uses thoracic impedance to obtain a thoracicfluid status signal. Therefore, the signal of interest in the presentpatent application would be deemed noise in the Hartley et al. U.S. Pat.No. 6,076,015, and vice-versa. However, both thoracic fluid status andrespiration are obtainable using the thoracic impedance detectiontechniques described in the Hartley et al. U.S. Pat. No. 6,076,015. Thepresent thoracic fluid status signal of interest is obtained from alower frequency (i.e., a “near-DC”) portion of the thoracic impedancesignal rather than the frequencies of the respiration signal describedin the Hartley et al. U.S. Pat. No. 6,076,015. In this document, the“near-DC” component of the thoracic impedance signal refers to thefrequencies below which respiration and cardiac contractionssignificantly influence the thoracic impedance signal. This near-DCcomponent of the thoracic impedance signal, therefore, typically refersto signal frequencies below a cutoff frequency having a value of about0.1 Hz, such as at signal frequencies between about 5×10⁻⁷ Hz and 0.05Hz, because the cardiac stroke and respiration components of thethoracic impedance signal lie at higher frequencies. Fluid accumulationin the thorax corresponds to a decrease in the near-DC thoracicimpedance. Conversely, fluid depletion in the thorax corresponds to anincrease in the near-DC thoracic impedance. As discussed above, fluidaccumulation may result from, among other things, pulmonary edema orpleural effusion, both of which may result from CHF.

In the example of FIG. 1, the system 100 also includes a controller 108.The controller 108 is typically a microprocessor or any other circuitthat is capable of sequencing through various control states such as,for example, by using a digital microprocessor having executableinstructions stored in an associated instruction memory circuit, amicrosequencer, or a state machine. In this example, the controller 108includes a digital signal processor (DSP) circuit 110. The digitalsignal processor circuit 110 performs any digital filtering or othersignal processing needed to extract from the thoracic impedance signal anear-DC desired thoracic fluid amount signal. The digital signalprocessor circuit 110, therefore, may implement one or more filtercircuits, and such filter circuits may be implemented as a sequence ofexecutable instructions, rather than by dedicated filtering hardware.

However, the present inventors have recognized that the near-DC thoracicimpedance signal is typically also affected by confounding factors otherthan the amount of fluid present in the thorax. One such confoundingfactor is any change in blood resistivity. Blood resistivity changes asa function of hematocrit in the blood. The hematocrit (Ht) or packedcell volume (PCV) is the proportion of blood that is occupied by redblood cells. It is typically between 0.35 and 0.52, and is slightlyhigher on average in males than in females. For example, when a patientis dehydrated, there will be less fluid in the patient's blood.Therefore, the patient's hematocrit level will increase, that is, thepatient's blood will include a higher percentage of other components,such as insulative red blood cells. This will increase the bloodresistivity, which, in turn, will affect the thoracic impedance signaleven through it is not necessarily associated with the extravascularfluid accumulation of pulmonary edema or pleural effusion. Other factorsthat are believed to possibly influence blood resistivity include thepatient's electrolyte level, certain medications in the blood, proteinsin the blood, or blood gas concentrations.

As an illustrative example, the above change in hematocrit percentagefrom 35% to 52% may correspond to a change in resistivity from about 140Ω·cm to about 200 Ω·cm. Such changes in blood resistivity will influencethe near-DC thoracic impedance measurement. This will confound anextravascular thoracic fluid amount determination using the near-DCthoracic impedance measurement, unless the extravascular thoracic fluidamount determination is corrected for such variations in bloodresistivity, if any. Measurement of variations in blood resistivity istypically affected by the frequency of the excitation signal that areused. At higher excitation frequencies, blood cells typically becomemore resistive.

Accordingly, the system in FIG. 1 illustrates a blood resistivitymeasurement circuit 106. The blood impedance measurement circuit 106receives a blood impedance measurement from electrodes that areassociated with blood (and preferably blood in the thorax) such as inresponse to a delivery of test energy by a blood impedance test energydelivery circuit 112. In one example, the blood impedance measurementcircuit 106 and the blood impedance test energy delivery circuit 112 areconfigured similar to the thoracic impedance measurement circuit 102 andthe thoracic impedance test energy delivery circuit 104, respectively,as discussed above, except for being connected to different electrodes.Using the blood impedance measurement, the controller 108 executes asequence of instructions to compute a blood resistivity correction 114.The blood resistivity correction 114 is applied to the thoracic fluidindication that is output by the digital signal processor circuit 110.This yields an adjusted thoracic fluid amount indication 116.

In FIG. 1, the thoracic impedance test energy delivery circuit 104 isillustrated separately from the blood impedance test energy deliverycircuit 112 to assist the reader's conceptualization. In practice, thesecircuits, or portions thereof, may be combined. The combined circuit maybe coupled to different electrodes for delivering the thoracic impedancetest energy than for delivering the blood impedance test energy.Similarly, in FIG. 1, the thoracic impedance measurement circuit 102 isillustrated separately from the blood impedance test energy deliverycircuit 112 to assist the reader's conceptualization. In practice, thesecircuits, or portions thereof, may be combined. The combined circuit maybe coupled to different electrodes for measuring the responsive voltagesfor the thoracic and blood impedance measurements, as discussed below.

FIG. 2 is a schematic illustration of one example in which portions ofthe system 100 are implemented in an implantable cardiac rhythmmanagement (CRM) or other implantable medical device (IMD) 200. In thisexample, the IMD 200 is coupled to a heart 202 using at least oneleadwire, such as a multielectrode leadwire 204. In this example, theleadwire 204 includes a tip electrode 206, a distal ring electrode 208,and a proximal ring electrode 210, each of which is disposed in theright ventricle of the heart 202. In this example, each of the tipelectrode 206, the distal ring electrode 208, and the proximal ringelectrode 210 is independently electrically connected to a correspondingseparate electrically conductive terminal within an insulating header212. The header 212 is affixed to a housing 214 carrying electroniccomponents of the IMD 200. In this example, the header 212 includes aheader electrode 216, and the housing 214 includes a housing electrode218.

In one example, thoracic impedance is sensed by delivering a testcurrent between: (1) at least one of the ring electrodes 208 or 210; and(2) the housing electrode 218, and a resulting responsive voltage ismeasured across the tip electrode 206 and the header electrode 216.Because the IMD 200 is typically pectorally implanted at some distanceaway from the heart 202, this electrode configuration injects the testcurrent over a substantial portion (but typically not the entireportion) of the patient's thorax, such that when the resulting voltagemeasurement is divided by the test current magnitude, it yields anindication of thoracic impedance. Using different electrodes fordelivering the current and for measuring the responsive voltage reducesthe component of the measured impedance signal that results from ohmiclosses in the leadwires to the test current delivery electrodes. Whilesuch a “four-point” probe is useful, it is not required. In otherexamples, a “three-point probe” (having three electrodes, with oneelectrode used for both test current delivery and responsive voltagemeasurement), or a “two-point probe” (having two electrodes, eachelectrode used for both test current delivery and responsive voltagemeasurement) are used. Moreover, other electrode combinations couldalternatively be used to implement a four-point probe. The abovefour-point probe description provides an illustrative example of onesuitable four-point probe configuration.

In one example, blood impedance is sensed by delivering a test currentbetween: (1) one of the distal ring electrode 208 or the proximal ringelectrode 210; and (2) the housing electrode 218. A resulting responsivevoltage is measured between: (1) the other of the distal ring electrode208 or the proximal ring electrode 210; and (2) the tip electrode 206.In this example, although the test current is injected across asubstantial portion of the patient's thorax, as discussed above, theresponsive voltage signal of interest is measured across electrodeswithin the same chamber of the patient's heart (or, alternatively,within the same blood vessel). Therefore, when the responsive voltagemeasurement is divided by the test current magnitude, it yields anindication of the blood impedance in the heart chamber rather than thethoracic impedance. The measured blood impedance is used to compensatethe measured thoracic impedance for changes in the blood impedance.

FIG. 3 is a block diagram illustrating generally another example inwhich portions of the system 100 are implemented in an implantable CRMor other IMD 300. The example of FIG. 3 includes an impedance teststimulus circuit 302 that, together with an impedance measurementcircuit 304, provides thoracic and blood impedance measurements. Inresponse to one or more control signals from the controller 108, anelectrode configuration multiplexer 306 couples these circuits to theappropriate electrodes for the particular thoracic or blood impedancemeasurement. In this example, the multiplexer 306 is also coupled to aheart signal sensing circuit 308, which includes sense amplifier orother circuits for detecting from particular electrodes intrinsicelectrical heart signals that include electrical depolarizationscorresponding to heart contractions. The multiplexer 306 is also coupledto a therapy circuit 310, such as a pulse delivery circuit fordelivering pacing, cardioversion, or defibrillation energy to particularelectrodes in response to one or more control signals received from thecontroller 108.

In the example of FIG. 3, the DSP circuit 110 processes the thoracicimpedance measurements from the impedance measurement circuit 304. TheDSP circuit 110 extracts a cardiac stroke signal or a respiration signalfrom the thoracic impedance signal, such as by using techniquesdescribed in the above-incorporated Hartley et al. U.S. Pat. No.6,076,015. One or both of the extracted cardiac stroke or respirationsignals is provided to a blood impedance measurement synchronizationcircuit 312. The synchronization circuit 312 includes one or morepeak-detector, level-detector, or zero-cross detector circuits tosynchronize the blood impedance measurement to the same sample point ofa cardiac contraction cycle or a respiration cycle. This reduces theeffect of variations in one or both of these cycles on the bloodimpedance measurement. Similarly, the measurements can be taken underthe same conditions with respect to posture or circadian cycle to reducethose effects on the blood impedance measurement. Posture can bedetected using an accelerometer or other posture sensor; circadian cyclecan be ascertained from a time-of-day indication provided by a clockcircuit within the controller 108. Alternatively, the cardiac cycleinformation is extracted from the heart signal sensing circuit 308,either by itself or in combination with information from the controller108 about when pacing or other stimulus pulses that evoke a responsiveheart contraction are issued. The controller 108 computes an adjustedthoracic fluid indication 116 from the measured thoracic impedance. Theadjusted thoracic fluid indication 116 is compensated for bloodresistivity variations using the blood resistivity correction 114obtained using the measured blood impedance. In a further example, theimplantable medical device 300 includes a telemetry circuit 314 thatcommunicates one of the blood-resistivity-compensated thoracic impedanceor the blood resistivity and thoracic impedance measurements to anexternal programmer 316 or the like for further processing, storage, ordisplay.

FIG. 4 is a flow chart illustrating generally one example of a method ofproviding a thoracic fluid amount indication that is compensated for anychanges in blood resistivity. At 400, a thoracic impedance is detected.This may be accomplished in a number of different ways. In oneillustrative example, such as described in Hartley et al. U.S. Pat. No.6,075,015, it includes injecting a four-phase carrier signal, such asbetween a housing electrode 218 and a ring electrode 208. In thisexample, the first and third phases are +320 microampere pulses that are20 microseconds long. The second and fourth phases are −320 microamperepulses that are 20 microseconds long. The four phases are repeated at 50millisecond intervals to provide a carrier test current signal fromwhich a responsive voltage can be measured. However, as discussedelsewhere in this document, because blood resistivity varies withexcitation frequency, a different excitation frequency may also be used.

The Hartley et al. U.S. Pat. No. 6,075,015 describes an exciter circuitfor delivering such a test current stimulus (however, the present systemcan alternatively use other suitable circuits, including an arbitrarywaveform generator that is capable of operating at different frequenciesor of mixing different frequencies to generate an arbitrary waveform).It also describes a signal processing circuit for measuring a responsivevoltage between a housing electrode 216 and a tip electrode 206. In oneexample, the signal processing circuit includes a preamplifier,demodulator, and bandpass filter for extracting the thoracic impedancedata from the carrier signal, before conversion into digital form by anA/D converter. Further processing is performed digitally, and isperformed differently in the present system 100 than in the Hartley etal. U.S. Pat. No. 6,075,015.

For example, the Hartley et al. U.S. Pat. No. 6,075,015 includes abandpass filter that receives the output of the A/D converter. Thepurpose of the highpass portion of the bandpass filter is to attenuatethe near-DC portion of the thoracic impedance signal, which is thesignal of interest to the present system 100. Therefore, the presentsystem 100 eliminates the highpass filter. The cutoff frequency of theremaining lowpass filter is selected to pass the near-DC portion of thethoracic impedance signal and attenuate higher frequency portions of thethoracic impedance signal, including the respiration and cardiac strokecomponents of the thoracic impedance signal. In one example, aprogrammable cutoff frequency lowpass filter is used. In anotherexample, an adaptive cutoff frequency lowpass filter is used, such thatthe cutoff frequency is moved to a higher frequency for higher values ofheart rate and respiration frequency, and the cutoff frequency is movedto a lower frequency for lower values of heart rate and respirationfrequency.

At 402 of FIG. 4, blood impedance is detected and measured. There are anumber of ways in which this can be done. In one example, the bloodimpedance measurement is performed in the same manner as the thoracicimpedance measurement, except that measurement of the responsive voltageis across two electrodes that are both typically located in the sameheart chamber or same blood vessel, such as between (1) one of thedistal ring electrodes 208 or the proximal ring electrode 210; and (2)the other of the distal ring electrode 208 or the proximal ringelectrode 210. Because the blood impedance is to be used to correct athoracic fluid indication, it is typically detected and measured at ornear the thorax. Alternatively, however, even an external bloodimpedance measurement could be used, if desired. In one example, theblood impedance is sampled under appropriate other conditions (e.g., ata like point in different cardiac cycles, at a like point in differentrespiration cycles, etc.).

At 404, a thoracic fluid amount indication is determined. There are anumber of ways in which this can be done. In one example, the thoracicfluid amount indication is given by the value of the near-DC thoracicimpedance signal, which may be averaged or otherwise filtered, ifdesired. In another example, a baseline value of this averaged orotherwise filtered near-DC thoracic impedance signal is obtained fromthe patient, and the thoracic fluid amount indication is given by thedifference of the near-DC thoracic fluid impedance value (with the sameor different averaging or filtering) from this baseline value.

At 406, the thoracic fluid amount indication obtained from the near-DCthoracic impedance is adjusted to compensate for changes in bloodresistivity. In one example, the adjusted thoracic fluid amountindication is given by:TFA_(adj)=TFA_(raw)·(ρ_(Blood, current))÷(ρ_(Blood, baseline)). In thisequation, TFA_(adj) is the adjusted value of the thoracic fluid amount,(ρ_(Blood, baseline)) is the baseline value of the blood resistivity,and (ρ_(Blood, current)) is the current value of the blood resistivity.In the present case, since the same electrodes are used for both thebaseline and current blood resistance measurements, the resistivityratio (ρ_(Blood, current))÷(ρ_(Blood, baseline)) is given by thecorresponding ratio of the blood resistances, i.e.,(Z_(Blood, current))÷(Z_(Blood, baseline)).

In a further example, such as where the implantable medical device 300optionally includes a posture sensor or detector 318, a separatebaseline impedance or resistivity is provided for different postures,since posture affects thoracic impedance measurements. In one example, aseparate baseline impedance or resistivity is stored for uprightpostures (e.g., sitting or standing) than for recumbent postures (e.g.,supine, prone, left lateral decubitus, right lateral decubitus). In afurther example, a separate baseline impedance or resistivity is storedfor one or more of the different subtypes of upright or recumbentpostures. In compensating the thoracic fluid amount indication, theposture compensation module 320 compensates a particular resistivitymeasurement by using a baseline resistivity that corresponds to thethen-current posture indicated by the postures detector 318. One exampleof a suitable posture detector 318 is a commercially available two-axisaccelerometer, such as Model No. ADXL202E, manufactured by AnalogDevices, Inc. of Norwood, Mass., USA.

The compensated thoracic fluid amount indication can be stored in theimplantable medical device 300 or transmitted to the external device316. Moreover, in one example, the implantable medical device 300 orexternal device 316 is capable of storing a history of the values of thethoracic fluid amount indication to assist the physician in managing theCHF state of the patient. In one example, the external device 316 iscapable of displaying a graph, histogram or other chart of such thoracicfluid amount values.

In a further example, the implantable medical device 300 or the externaldevice 316 determines whether heart failure decompensation, pulmonaryedema, or pleural effusion is present, such as by comparing an increasein the blood-resistivity-compensated thoracic fluid amount indication toa corresponding first threshold value to deem one or more of theseconditions to be present.

In yet a further example, the implantable medical device 300 or theexternal device 316 predicts whether heart failure decompensation,pulmonary edema, or pleural effusion is likely to become present in thefuture, such as by comparing an increase in theblood-resistivity-compensated thoracic fluid amount indication to acorresponding second threshold value to deem one or more of theseconditions to be likely in the future. The second threshold used for thecondition prediction may be different from the first threshold used forthe condition detection. In one example, the second threshold valuereflects a smaller increase in the thoracic fluid amount indication thanthe first threshold value.

In yet a further example, the implantable medical device 300 adjusts atherapy to the patient using the thoracic fluid amount indication. Inone example, an increase in the thoracic fluid amount indicationtriggers an increase in a rate at which pacing pulses are delivered tothe heart. In another example, a change in the thoracic fluid amountindication results in altering another programmable parameter of cardiacpacing or cardiac resynchronization therapy, such as, for example,atrioventricular (AV) delay, particular cardiac stimulation sites,interventricular delay, or intraventricular delay. In a further example,a change in the thoracic fluid amount indication triggers the providingof a warning or other indication to the patient to adjust a medicationlevel (for example, a diuretic).

Another application for the present systems, devices, and methods is inanemia detection. Anemia is a pathological condition that is oftenpresent in CHF patients. Diagnosing and treating anemia will improve apatient's cardiac function. Therefore, there is a need to detect anemiain CHF patients, for example, to communicate a diagnosis regarding theanemia status to a CHF patient's health care provider.

FIG. 5 is a flow chart illustrating generally one example of an anemiadetection method. At 500, a baseline blood impedance is established. Inone example, this includes obtaining one or more near-DC blood impedancemeasurements (typically taken within the same blood vessel or heartchamber) such as described above with respect to 402 of FIG. 4. In oneexample, the baseline blood impedance is established by computing acentral tendency (e.g., average, median, low-pass filtered, etc.) valueof a series of such measured blood impedances over a desired timeinterval (for example, one month).

At 502, a current blood impedance is measured. This near-DC bloodimpedance measurement is typically performed in the same manner andlocation as described above for establishing the baseline. At 504, thecurrent blood impedance is compared to the baseline blood impedance. Asdescribed above, a higher percentage of red blood cells tends toincrease blood impedance. Therefore, when the current blood impedancefalls far enough below the baseline blood impedance, then anemia may beindicated. Therefore, in one example, if the current blood impedancefalls below the baseline blood impedance by at least an offset thresholdvalue, then anemia is declared to be present at 506. In one example, theoffset value is a fixed or programmable percentage of the baseline bloodimpedance (e.g., 5%, 10%, 20%, etc.). The offset value is typically setto prevent normal physiological variations in blood impedance fromtriggering an anemia detection. In another example, such as by choosinga different threshold value, the comparison predicts that anemia islikely to occur (e.g., if the blood impedance falls at least 10% belowits baseline value, then future anemia is predicted; if the bloodimpedance then falls at least 20% below its baseline value, then presentanemia is declared).

In one further example, if anemia is predicted or declared present, thatinformation is telemetered or otherwise communicated to the patient'shealth care provider from the implantable medical device, such as byproviding such information to an external device for storage or display.In one example, such communication takes place the next time that theimplantable medical device is interrogated by a programmer or otherexternal interface. In another example, such the implantable medicaldevice itself initiates a telemetric or other communication of suchinformation to an external device. In yet a further example, an anemiawarning is provided to the patient, either directly by the implantablemedical device (e.g., an audible warning), or via an external interfacedevice.

As discussed above, measurement of variations in blood resistivity istypically affected by the frequency of the excitation signal that areused. At higher excitation frequencies, blood cells typically becomemore resistive. Therefore, to yield a more sensitive measurement ofanemia, it may be desirable to use a higher excitation frequency thanwould be used for detecting thoracic impedance, and for correcting theresulting thoracic impedance measurements for changes in bloodresistivity. Alternatively, such as for measuring thoracic fluid status,if a change in blood resistivity exceeds a certain threshold value then,in one example, the system automatically switches to a lower excitationfrequency that is affected less by changes in blood resistivity.

Although much of the above discussion has emphasized correcting near-DCthoracic impedance measurements to account for changes in bloodresistivity, hematocrit-related blood resistivity changes may alsoaffect higher frequency components of the thoracic impedance signal(e.g., respiration components, cardiac stroke components, etc.),somewhat analogous to the way in which patient posture can affect suchhigher frequency components of the thoracic impedance signal. Aspects ofthe present blood resistivity measurement and correction techniques mayalso be used for correcting such higher-frequency components of thethoracic impedance signal. However, the effects of blood resistivitychanges at higher frequency may be nonlinear, making correction with asingle multiplicative correction factor difficult or impossible.Therefore, a nonlinear correction function may be used, if needed. Sucha nonlinear correction function may be empirically determined. In oneexample, the nonlinear correction function may be implemented as alookup table. Moreover, the higher-frequency components of the thoracicimpedance signal may be used to infer thoracic fluid status even much ofthe above discussion focused on particular examples that extract athoracic fluid status signal from the near-DC component of the thoracicimpedance signal.

It is to be understood that the above description is intended to beillustrative, and not restrictive. For example, the above-describedembodiments (and/or aspects thereof) may be used in combination witheach other. Many other embodiments will be apparent to those of skill inthe art upon reviewing the above description. The scope of the inventionshould, therefore, be determined with reference to the appended claims,along with the full scope of equivalents to which such claims areentitled. In the appended claims, the terms “including” and “in which”are used as the plain-English equivalents of the respective terms“comprising” and “wherein.” Also, in the following claims, the terms“including” and “comprising” are open-ended, that is, a system, device,article, or process that includes elements in addition to those listedafter such a term in a claim are still deemed to fall within the scopeof that claim. Moreover, in this document and in the following claims,the terms “first,” “second,” and “third,” etc. are used merely aslabels, and are not intended to impose numerical requirements on theirobjects.

1. A method comprising: detecting a thoracic impedance signal of athorax of a subject; detecting a blood resistivity signal by sensingbetween at least two intravascular or intracardiac electrodes disposedin the same chamber of the heart or the same blood vessel; anddetermining a thoracic fluid indication using the thoracic impedancesignal, the determining the thoracic fluid indication including usingthe blood resistivity signal to reduce or eliminate an effect of achange in the blood resistivity on the thoracic fluid indication.
 2. Themethod of claim 1, further comprising filtering the thoracic impedancesignal to obtain a near-DC thoracic impedance signal, and in which thethoracic fluid indication is generated at least in part by using thenear-DC thoracic impedance signal.
 3. The method of claim 2, in whichthe filtering the thoracic impedance signal includes attenuating orremoving frequency components above about 0.05 Hz.
 4. The method ofclaim 2, in which the filtering the thoracic impedance signal includesattenuating or removing a cardiac stroke component of the thoracicimpedance signal.
 5. The method of claim 2, in which the filtering thethoracic impedance signal includes attenuating or removing a respirationcomponent of the thoracic impedance signal.
 6. The method of claim 2, inwhich the filtering the thoracic impedance signal includes accountingfor posture.
 7. The method of claim 2, in which the filtering thethoracic impedance signal includes using a variable lowpass cutofffrequency filter.
 8. The method of claim 1, in which the detecting thethoracic impedance signal and the determining the thoracic fluidindication are performed using an implantable medical device.
 9. Themethod of claim 1, in which the detecting the thoracic impedance signalcomprises: delivering a test current from first and second implantableelectrodes; and measuring a resulting voltage in response to the testcurrent from third and fourth implantable electrodes.
 10. The method ofclaim 9, in which at least one of the first and second implantableelectrodes is the same electrode as the third and fourth implantableelectrodes.
 11. The method of claim 9, in which the first and secondimplantable electrodes are different electrodes from the third andfourth implantable electrodes.
 12. The method of claim 9, in which thedelivering the test current includes delivering a carrier signal. 13.The method of claim 1, in which the detecting the thoracic impedancesignal includes using at least one cardiovascular electrode.
 14. Themethod of claim 1, in which the detecting the thoracic impedance signalincludes using at least one electrode located on a housing of animplantable medical device.
 15. The method of claim 1, in which thedetecting the thoracic impedance signal includes using at least oneelectrode located on a substantially electrically insulating header ofan implantable medical device.
 16. The method of claim 1, in which thedetecting the blood resistivity signal includes using first and secondintravascular electrodes.
 17. The method of claim 1, in which thedetecting the blood resistivity signal includes: delivering a testcurrent between first and second electrodes, in which the first andsecond electrodes are both located within single heart chamber or bloodvessel; and measuring a resulting voltage in response to the testcurrent.
 18. The method of claim 1, in which the detecting the bloodresistivity includes measuring blood resistivity using a volume of bloodthat is substantially independent of a degree of fluid present in thethorax.
 19. The method of claim 1, in which the detecting the bloodresistivity includes measuring the blood resistivity at like timesduring at least one of a cardiac cycle and a respiratory cycle.
 20. Themethod of claim 1, in which the determining a thoracic fluid indicationusing the thoracic impedance signal includes: measuring a first thoracicimpedance value at a first time; measuring a first blood resistivityvalue at a second time that is close to the first time; measuring asecond thoracic impedance value at a third time; and measuring a secondblood resistivity value at a fourth time that is close to the thirdtime; and normalizing, using the first and second blood resistivityvalues, the second thoracic impedance value to the first thoracicimpedance value.
 21. The method of claim 20, in which the normalizingincludes multiplying the second thoracic impedance value by a ratio ofthe first and second blood resistivity values.
 22. The method of claim1, in which the determining a thoracic fluid indication using thethoracic impedance signal includes: measuring a baseline first bloodresistivity value; measuring a first thoracic impedance value and acorresponding second blood resistivity value; and computing a secondthoracic impedance value using the first thoracic impedance value andthe first and second blood resistivity values.
 23. The method of claim22, in which the computing the second thoracic impedance value includesmultiplying the first thoracic impedance value by a ratio of the firstblood resistivity value to the second blood resistivity value.
 24. Themethod of claim 1, further comprising: storing a history of thoracicfluid measurements; and determining whether heart failure decompensationis present using the history of thoracic fluid measurements to determinewhether a change in thoracic fluid has occurred.
 25. The method of claim1, further comprising: storing a history of thoracic fluid measurements;and predicting heart failure decompensation using the history of thethoracic fluid measurements to determine whether a change in thoracicfluid has occurred.
 26. The method of claim 1, further comprising:storing a history of thoracic fluid measurements; and determiningwhether pulmonary edema is present using the history of thoracic fluidmeasurements to determine whether a change in thoracic fluid hasoccurred.
 27. The method of claim 1, further comprising: storing ahistory of thoracic fluid measurements; and predicting pulmonary edemausing the history of thoracic fluid measurements to determine whether achange in thoracic fluid has occurred.
 28. The method of claim 1,further comprising: storing a history of thoracic fluid measurements;and determining whether pleural effusion is present using the history ofthoracic fluid measurements to determine whether a change in thoracicfluid has occurred.
 29. The method of claim 1, further comprising:storing a history of thoracic fluid measurements; and predicting pleuraleffusion using the history of thoracic fluid measurements to determinewhether a change in thoracic fluid has occurred.
 30. The method of claim1, further including transmitting information about the thoracic fluidindication from an implantable medical device to an external device. 31.The method of claim 30, further including displaying the informationabout the thoracic fluid indication on the external device.
 32. Themethod of claim 30, further including storing the information about thethoracic fluid indication in the external device.
 33. The method ofclaim 1, further including providing therapy to the subject, the therapydetermined at least in part using the thoracic fluid indication.
 34. Themethod of claim 1, in which the using the blood resistivity signal toreduce or eliminate an effect of a change in the blood resistivity onthe thoracic fluid indication includes: measuring a posture of thepatient; storing a first baseline blood resistivity corresponding to afirst posture; storing a second baseline blood resistivity correspondingto a second posture that is different from the first posture; andcompensating the thoracic fluid indication by selecting and using theone of the first and second baseline blood resistivities thatcorresponds to the then-current posture of the patient.
 35. The methodof claim 34, in which the first posture is an upright posture and thesecond posture is a recumbent posture.
 36. A method of using animplantable medical device, the method comprising: detecting a thoracicimpedance signal of a thorax of a subject using implantable electrodesto deliver a test current and measure a responsive voltage; detecting ablood resistivity signal, sensed between at least two electrodesdisposed in the same chamber of the heart or the same blood vesselwithin a heart chamber or blood vessel, filtering the thoracic impedancesignal to substantially remove frequency components above 0.05 Hz toobtain a near-DC thoracic impedance signal; and determining a thoracicfluid indication using the thoracic impedance signal, the determiningthe thoracic fluid indication including compensating the thoracicimpedance signal for changes in blood resistivity.
 37. The method ofclaim 36, in which the compensating comprises multiplying a thoracicimpedance signal value by a ratio of a baseline blood resistivity to ablood resistivity measured close in time to a time when the thoracicimpedance signal value was measured.
 38. The method of claim 36, furthercomprising: storing a history of thoracic fluid measurements; anddetermining whether at least one of heart failure decompensation,pulmonary edema, and pleural effusion is present using the history ofthoracic fluid measurements to determine whether a change in thoracicfluid has occurred.
 39. A system comprising: an implantable medicaldevice, including: a thoracic impedance measurement circuit, to providea thoracic impedance signal; a blood resistivity measurement circuit, toprovide a blood resistivity signal sensed from at least twointravascular or intracardiac electrodes disposed in the same chamber ofthe heart or the same blood vessel; and a controller, coupled to theblood resistivity measurement circuit, the controller operable todetermine a thoracic fluid indication using the thoracic impedancesignal, including using the blood resistivity signal to reduce oreliminate an effect of a change in the blood resistivity on the thoracicfluid indication.
 40. The system of claim 39, in which the thoracicimpedance measurement circuit includes: a test current circuit todeliver a test current to first and second implantable electrodes; and avoltage measurement circuit to measure a resulting voltage between thirdand fourth implantable electrodes.
 41. The system of claim 40, furtherincluding the at least one of the first and second implantableelectrodes and at least one of the third and fourth implantableelectrodes, and in which at least one of the first and secondimplantable electrodes is the same electrode as the third and fourthimplantable electrodes.
 42. The system of claim 40, further includingthe at least one of the first and second implantable electrodes and atleast one of the third and fourth implantable electrodes, and in whichthe first and second implantable electrodes are different electrodesfrom the third and fourth implantable electrodes.
 43. The system ofclaim 40, in which the test current circuit includes a carrier signalgenerator circuit.
 44. The system of claim 39, further including atleast one cardiovascular leadwire electrode to detect the thoracicimpedance signal.
 45. The system of claim 39, in which the implantablemedical device includes a housing, and in which the housing includes atleast one electrode to detect the thoracic impedance signal.
 46. Thesystem of claim 45, in which implantable medical device includes atleast one substantially electrically insulating header attached to thehousing, and in which the header includes at least one electrode todetect the thoracic impedance signal.
 47. The system of claim 39,further comprising first and second cardiovascular electrodes to detectthe blood resistivity signal.
 48. The system of claim 47, in which thefirst and second cardiovascular electrodes are arranged with respect toeach other to be disposed within the same heart chamber or blood vessel.49. The system of claim 47, further including a sense amplifier todetect intrinsic heart signals corresponding to each cardiac cycle of asubject, and in which the blood resistivity measurement circuit includesa synchronization circuit to synchronize blood resistivity measurementsto at least one of (1) like phases of different cardiac cycles; and (2)like phases of different respiration cycles.
 50. The system of claim 39,further including a frequency selective filter circuit, to receive thethoracic impedance signal, the frequency selective filter circuitproviding a near-DC filtered thoracic impedance signal.
 51. The systemof claim 50, in which the filter circuit includes a lowpass filtercircuit including at least one lowpass pole at a frequency of about 0.05Hz.
 52. The system of claim 50, in which the filter circuit includes alowpass filter circuit including at least one lowpass pole at afrequency that attenuates or removes a cardiac stroke component of thethoracic impedance signal.
 53. The system of claim 50, in which thefilter circuit includes a lowpass filter circuit including at least onelowpass pole at a frequency that attenuates or removes a respirationcomponent of the thoracic impedance signal.
 54. The system of claim 50,in which the filter circuit includes a lowpass filter circuit includingat least one variable-frequency lowpass pole.
 55. The system of claim39, further comprising: a posture sensor, to provide a posture signal;and a posture compensation module, operable to compensate the thoracicfluid indication using the posture signal.
 56. The system of claim 55,in which the posture compensation module includes different baselineblood resistivity measurements corresponding to different postures. 57.The system of claim 39, in which the controller includes: a first memorylocation to store a first thoracic impedance value measured at a firsttime; a second memory location to store a first blood resistivity valuemeasured at a second time that is close to the first time; a thirdmemory location to store a second thoracic impedance value measured at athird time; and a fourth memory location to store a second bloodresistivity value measured at a fourth time that is close to the secondtime; and a normalization module to normalize, using the first andsecond blood resistivity values, the second thoracic impedance value tothe first thoracic impedance value.
 58. The system of claim 57, in whichthe normalization module includes an arithmetic logic unit (ALU) thatmultiplies the second thoracic impedance value by a ratio of the firstand second blood resistivity values.
 59. The system of claim 39, inwhich the controller circuit includes: an averaging circuit to measure afirst blood resistivity value; a first memory location to store a firstthoracic impedance value; a second memory location to store a secondblood resistivity value that corresponds to the first thoracic impedancevalue; and in which the controller circuit is operable to compute asecond thoracic impedance value using the first thoracic impedance valueand the first and second blood resistivity values.
 60. The system ofclaim 59, in which the controller includes a multiplier circuit tomultiply the first thoracic impedance value by a ratio of the firstblood resistivity value to the second blood resistivity value.
 61. Thesystem of claim 39, further comprising: a memory configured to store ahistory of thoracic fluid measurements; and a heart failuredecompensation detection or prediction module operable to determinewhether heart failure decompensation is present or likely to occur usingthe history of thoracic fluid measurements to determine whether a changein thoracic fluid has occurred.
 62. The system of claim 61, in which thememory and the decompensation detection or prediction module are locatedin the implantable medical device.
 63. The system of claim 61, in whichthe memory and the decompensation detection or prediction module arelocated in an external device.
 64. The system of claim 39, furthercomprising: a memory configured to store a history of thoracic fluidmeasurements; and a pulmonary edema detection or prediction moduleoperable to determine whether pulmonary edema is present or likely tooccur using the history of thoracic fluid measurements to determinewhether a change in thoracic fluid has occurred.
 65. The system of claim64, in which the memory and the pulmonary edema detection or predictionmodule are located in the implantable medical device.
 66. The system ofclaim 64, in which the memory and the pulmonary edema detection orprediction module are located in an external device.
 67. The system ofclaim 39, further comprising: a memory configured to store a history ofthoracic fluid measurements; and a pleural effusion detection orprediction module operable to determine whether pleural effusion ispresent or likely to occur using the history of thoracic fluidmeasurements to determine whether a change in thoracic fluid hasoccurred.
 68. The system of claim 67, in which the memory and thepleural effusion detection or prediction module are located in theimplantable medical device.
 69. The system of claim 67, in which thememory and the pleural effusion detection or prediction module arelocated in an external device.
 70. The system of claim 39, furtherincluding an external device operable to be communicatively coupled tothe implantable medical device to receive information about the thoracicfluid indication from the implantable medical device.
 71. The system ofclaim 70, in which the external device includes a display device todisplay the information about the thoracic fluid indication.
 72. Thesystem of claim 70, in which the external device includes a storagedevice to store the information about the thoracic fluid indication. 73.The system of claim 39, further including a therapy circuit, coupled tothe controller, the therapy circuit operable to provide a therapy to asubject, the therapy determined at least in part using the thoracicfluid indication from the controller.
 74. A system comprising: animplantable medical device, including: a thoracic impedance measurementcircuit, to provide a thoracic impedance signal; a frequency-selectivefilter circuit, coupled to the thoracic impedance measurement circuit toreceive the thoracic impedance signal, the frequency selective filtercircuit including at least one lowpass pole providing a near-DC filteredthoracic impedance signal, the at least one lowpass pole substantiallyattenuating or removing at least one of a heart contraction componentand a respiration component of the thoracic impedance signal; a bloodresistivity measurement circuit, to provide a blood resistivity signal,sensed from at least two intravascular or intracardiac electrodesdisposed in the same chamber of the heart or the same blood vessel, fromwhich a blood resistivity measurement is obtained, and a controller,coupled to the filter circuit and the blood resistivity measurementcircuit, the controller operable to determine a thoracic fluidindication using the filtered thoracic impedance signal, including usingthe blood resistivity signal to reduce or eliminate an effect of achange in the blood resistivity on the thoracic fluid indication, thethoracic fluid indication determined by multiplying a thoracic impedancesignal value by a ratio of a baseline blood resistivity to a bloodresistivity measured close in time to a time when the thoracic impedancesignal value was measured.
 75. The system of claim 74, furthercomprising: a memory storage device operable to store a history ofthoracic fluid measurements; and means for determining whether at leastone of heart failure decompensation, pulmonary edema, and pleuraleffusion is present using the history of thoracic fluid measurements todetermine whether a change in thoracic fluid has occurred.
 76. A systemcomprising: an implantable medical device, including: a thoracicimpedance measurement circuit, to provide a thoracic impedance signal; afrequency selective filter circuit, coupled to the thoracic impedancemeasurement circuit to receive the thoracic impedance signal, thefrequency selective filter circuit providing a near-DC filtered thoracicimpedance signal; a blood resistivity measurement circuit, to provide ablood resistivity signal sensed from at least two intravascular orintracardiac electrodes disposed in the same chamber of the heart or thesame blood vessel; means for determining a thoracic fluid indicationusing the filtered thoracic impedance signal; and means for reducing oreliminating an effect of a change in blood resistivity on the thoracicfluid indication.
 77. The system of claim 76, further comprising: amemory storage device operable to store a history of thoracic fluidmeasurements; and means for determining whether at least one of heartfailure decompensation, pulmonary edema, and pleural effusion is presentusing the history of thoracic fluid measurements to determine whether achange in thoracic fluid has occurred.
 78. A system comprising: animplantable medical device, including: first and second electrodeslocated within the same blood vessel or heart chamber; a bloodresistivity measurement circuit, to provide a blood resistivity signalobtained between the first and second electrodes at different first andsecond times; and a controller, coupled to the blood resistivitymeasurement circuit, the controller operable to determine an indicationor prediction of anemia by comparing a current blood resistivity to astored baseline blood resistivity value.
 79. The system of claim 78, inwhich the blood resistivity measurement circuit includes: a test currentcircuit to deliver a test current to first and second implantableelectrodes; and a voltage measurement circuit to measure a resultingvoltage between third and fourth implantable electrodes.
 80. The systemof claim 78, further comprising a heart signal sensing circuitconfigured to synchronize the first and second times to like portions ofdifferent cardiac cycles.
 81. The system of claim 78, further comprisinga thoracic impedance measurement circuit configured to synchronize thefirst and second times to like portions of different respiration cycles.82. The system of claim 78, further comprising a posture sensor and aposture compensation module configured to store different baseline bloodresistivities corresponding to different postures obtained from theposture sensor.
 83. A system comprising: means for detecting a thoracicimpedance signal of a thorax of a subject; means for detecting a bloodresistivity signal sensed between at least two intravascular orintracardiac electrodes disposed in the same chamber of the heart or thesame blood vessel; and means for determining a thoracic fluid indicationusing the thoracic impedance signal, the determining the thoracic fluidindication including using the blood resistivity signal to reduce oreliminate an effect of a change in the blood resistivity on the thoracicfluid indication.